Vectors or carriers are actively developed for positively delivering substances such as proteins, agents, or nucleic acids to target sites in individual organisms. For example, viral vectors such as a retrovirus, an adenovirus, and an adeno-associated virus have each been developed as a vector for introducing a gene of interest into target cells. However, viral vectors have problems such as difficult large-scale production, antigenicity, and toxicity; thus, attention has been drawn to a lipid membrane structure typified by a liposome vector and a peptide carrier which have such problems reduced.
The liposome vector is a lipid membrane structure using an artificially prepared lipid bilayer membrane as a basic configuration and has the ability to encapsulate various substances for delivery into target cells. The liposome vector has the advantage of encapsulating a substance and thereby protecting it from in vivo decomposition or metabolism and the advantage of preventing the substance from acting at sites other than a target site (side effects) in addition to the advantage of being improved in tropism for a target site by introducing a functional molecule such as an antibody, a protein, or a sugar chain into the surface thereof.
When a high-molecular compound such as a lipid membrane structure encapsulating a substance such as a protein, an agent, or a nucleic acid or a peptide carrier binding to a protein, an agent, a nucleic acid, or the like is administered into the blood, however, it represents a big challenge to cause the compound to reach from the blood to a target site. Vascular endothelial cells form tight junction between the cells in many tissues and the gap between vascular endothelial cells is as very narrow as about 0.4 nm to about 4 nm; thus, it is difficult for the high-molecular compound administered into the blood to reach the target site through the gap.
Accordingly, lipid membrane structures or peptide carriers are researched and developed which each reach the target site across a vascular endothelial cell layer forming tight junction; for example, the development has been performed of a peptide promoting transcytosis in epithelial cells, selected from albumin, GP60 as an albumin-binding protein, and an anti-GP60 antibody (Patent Literature 1), a peptide promoting transcytosis in the blood-brain barrier, comprising the binding part of megalin as an endocytosis receptor (Patent Literature 2), a method involving co-administrating an antisense oligonucleotide inhibiting the synthesis of occludin as a tight junction-forming protein and a lipid membrane structure or a peptide carrier (Patent Literature 3), and the like.